Photodynamic therapy and cancer: a brief sightseeing tour

Photodynamic therapy (PDT) combines a drug (a photosensitiser or photosensitising agent) with a specific type of light to kill cancer cells. It is a minimally invasive treatment, with great potential in malignant disease and premalignant conditions. Following the administration of the photosensitiser, light of the appropriate wavelength is directed onto the abnormal tissue where the drug has preferentially accumulated. Upon light activation, the photosensitiser transfers its excess energy to molecular oxygen to produce an excited state (i.e., the highly reactive singlet oxygen) that causes oxidative damage at the site of its generation. The energy transfer occurs either directly to oxygen or through an indirect mechanism that requires the formation of intermediate radical species. Many photosensitisers have been developed, but only a few have been approved for therapy in humans. Basic research in model systems (animals, cell lines) has unravelled some fundamental cellular processes involved in the cell response to PDT. The exploitation of relevant molecular observations, the discovery and introduction of new sensitisers, the progress in the light delivery systems and light dosimetry are all concurring to the increase of PDT therapeutic efficacy. However, this field has not yet reached maturity. This review briefly analyses the relevant properties of most photosensitisers and their field of application. Special attention is dedicated to the effects observed in model cancer systems; speculation and suggestions of possible future research directions are also offered.